Voretigene Neparvovec Gene Therapy in Clinical Practice: A 12-Month, Single-Center, In-Depth Analysis of Beneficial and Adverse Drug Effects

Purpose: To investigate the effects of voretigene neparvovec (VN) treatment in patients with RPE65-related retinal dystrophies, with particular focus on chorioretinal atrophy (CRA) and its impact on visual function. Methods: Twenty-five patients treated with VN were evaluated over a 12-month follow-up and stratified according to the presence of postoperative CRA, classified into nummular, mixed and touchdown patterns. Results: Best-corrected visual acuity (BCVA) improved by a median of 11 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (P < 0.001). Semiautomated kinetic visual field (SKVF) showed a significant (P < 0.001) enlargement for both I4e and III4e stimulus sizes. Fullfield stimulus threshold (FST) results also improved significantly (P < 0.001), with median changes of -2.79 (-3.61 to -2.11) log cd·s/m2 for white, -3.02 (-4.05 to -2.24) log cd·s/m2 for blue, and -1.30 (-1.76 to -0.74) log cd·s/m2 for red stimuli. Fifteen patients developed CRA (60%), of whom nine exhibited progressive nummular/mixed CRA, which significantly expanded over time (P < 0.001), and six showed the localized, non-progressive touchdown pattern. Younger age and a clinical diagnosis of LCA were significantly associated with nummular/mixed CRA. No significant differences in BCVA or FST improvements were found between nummular/mixed and touchdown/no-CRA groups. Conversely, significant SKVF I4e enlargement occurred only in the touchdown/no-CRA subgroup (1624°2, 0-6278; P < 0.001), with a significant intergroup difference (P = 0.003). Conclusions: Our findings confirmed the visual function improvements following VN and the relatively high prevalence of CRA, which seems to impact negatively only on SKVF enlargement. Translational Relevance: These findings are useful to better understand risks and benefits of VN gene therapy.